One‐Pot Four‐Component Synthesis of Thieno[2,3‐d]pyrimidin‐4‐amines via Sequential Gewald/Cyclocondensation Reactions

Abstract

A one‐pot four‐component synthesis of thieno[2,3‐d]pyrimidin‐4‐amines via sequential Gewald/cyclocondensation reactions is described. 2‐Aminothiophene‐3‐carbonitriles obtained from the Gewald reaction between cyclic ketones, malononitrile, and sulfur underwent a condensationcyclization reaction with benzonitriles under solvent‐free conditions to afford the title compounds in excellent yields.

Synthesis, characterization, and molecular structure investigation of new tetrahydrobenzo[b]thiophene-based Schiff bases: A combined experimental and theoretical study

“…The starting material 2-amino-4, 5, 6, 7tetrahydrobenzo[b]thiophene-3carbonitrile 1 was prepared according to the literature method [59,60]. First, the reaction between this compound and 2nitrobenzaldehyde 2a was selected as the test reaction to determine suitable reaction conditions.…”

Diversification Via Coupling Reactions and Biological Activities of Pyrimidine Derivatives

“…[22,23] In the same way, the Gewald synthesis affords a way to make substituted pyrimidines by reacting thioureas with unsaturated carbonyl substances. [24][25][26] These synthetic techniques have made the creation of novel pyrimidine-based molecules with improved pharmacological characteristics easier. In general, pyrimidines play a significant role in both biology and pharmacology.…”

“…The Biginelli reaction, which uses a multicomponent response involving a ketoester, aldehyde, and urea or thiourea to generate the pyrimidine ring system, is a well‐known technique for their synthesis [22,23] . In the same way, the Gewald synthesis affords a way to make substituted pyrimidines by reacting thioureas with unsaturated carbonyl substances [24–26] . These synthetic techniques have made the creation of novel pyrimidine‐based molecules with improved pharmacological characteristics easier.…”

Green methodologies for the synthesis of 2-aminothiophene

“…Implementations in photovoltaic cells have also been related (Stylianakis et al 2010 ). Moreover, 2-aminothiophene was considered as a central scaffold on which modifications could be realized to obtain more complex molecules (Adib et al 2015 ; Abdelwahab et al 2016 ; Abaee et al 2017 ; El-Mekabaty et al 2017 ). Despite their importance in various application fields, only a few reviews on their methods of synthesis have been published, and if they do, they usually focus on the Gewald methodology (Nylund and Johansson 2010 ; Puterová et al 2010 ; Huang and Dömling 2011 ; Bello Forero et al 2013 ).…”